Designer kids are a matter of time

How to make Designer babies

Sergey Yakovenko, Forbes, 12.12.2018

The announcement that a Chinese scientist edited the genome of a human embryo for the first time opened a new era in the fight against hereditary diseases. However, many methods of reproductive medicine, which have been successfully used in the world for a long time, allow to take care of the genetic health of children.

At the end of November, Chinese geneticist He Jiankui announced that he had managed to edit the genomes of human embryos. Twin girls were born, and one of them, thanks to an edited version of the CCR 5 gene, turned out to be resistant to HIV infection. The world community reacted to the news quite sharply, questions were raised about the ethical permissibility of such experiments.

In fact, Dr. He's experience combines two technologies that have been successfully used in biology and medicine for a long time. One of them is gene editing using the CRISPR–cas9 system, which is well-developed in application to mammalian embryos. The second part is the technique of in vitro fertilization, with the help of which many millions of healthy children have already appeared in the world.

When it became known about the success of Chinese geneticists, Russian molecular biologists turned to the Altravita clinic, asking if we had any patients who needed genomic editing services. They made it clear that they are ready to provide the molecular biological part of the technology. There are no such patients yet, but, apparently, their appearance is only a matter of time.

Currently, Russian legislation does not regulate such activities in any way. However, in most clinics providing IVF services, there are ethics councils, which, apparently, in the absence of legislative norms, will decide on the admissibility of such procedures in each specific case. Obviously, the main criterion will be the question of the severity of the potential consequences for the child's health, which the genomic editing procedure is designed to prevent. These consequences will be compared with the risk of the procedure itself, so as not to violate the main principle of medicine: "Do no harm."

Anyway, it is premature to talk about the widespread use of this method. In this article I would like to tell you that even traditional techniques of reproductive medicine and genetic analysis allow you to program the genetic health of an unborn child. These methods are quite ethical, well-developed and widely used everywhere in the world.

Genetic risk

Each person carries pathogenic mutations in their genes. Each gene is represented by two copies, one on each of the paired chromosomes, and for the development of a genetic disease, as a rule, it is necessary that mutations in the same gene inherited from both parents meet in one child. The frequency of carriage can be quite high (for example, pathogenic alleles of cystic fibrosis are carried by up to 5% of the population), but "meetings" of mutations in the same gene occur much less frequently.

Nevertheless, in general, genetic diseases are much more widespread than we would like to think. There are about 7000 different types of genetic diseases, of which 50% fall on children. 350 million people worldwide suffer from rare diseases, of which 80% are genetic. 30 million people in Europe and one in ten in the USA are trying to fight the disease. For clarity: if all these people lived in one place, it would be the third country in the world in terms of population. In the first year of life, 35% of newborns die due to genetic diseases. Approximately 6% of the requests received by the Information Center for Genetic and Rare Diseases (SARR) are not diagnosed.

There are factors that significantly increase the risk of hereditary disease. These are primarily closely related marriages, when there is a high probability that both parents carry a mutation in the same gene. The same problem is observed in isolates, that is, small settlements that have been isolated from the main population for a long time and cut off from gene migration. Another factor is the family history of hereditary diseases. Finally, the mature age of parents greatly increases the risk of having a child with aneuploidy – an incorrect number of chromosomes in cells.

Modern techniques of genetic analysis can significantly reduce, and sometimes completely eliminate these risks. If you approach child planning consciously, then any married couple should understand what achievements of biomedicine are at their disposal.

Natural fertilization

The most obvious way to take care of a child's genetic health is to decode the genomes of both parents to exclude the presence of mutations in the same genes. The number of people in the modern world who turn to commercial genomics services is doubling every year.

In addition, modern technologies make it possible to monitor the state of the genome of an already conceived and developing embryo. A non-invasive prenatal test has been developed, which examines the extracellular DNA of the fetus, which circulates in the woman's blood during pregnancy. This method is completely safe for the embryo, since a sample of a woman's venous blood is sufficient for analysis, and penetration into the uterine cavity does not occur. However, the method has certain limitations. The analyzed DNA comes from the placenta, and in about 1% of cases, genetic diseases have a mosaic nature, when the placenta and the embryo are genetically different. Because of this, a non-invasive method can give false positive and false negative results.

To check, an invasive test is performed – puncture of the amniotic membrane and taking a sample of the fluid filling the amnion cavity, which protects the fetus from damage. An invasive test is resorted to, for example, in cases where ultrasound indicates developmental disorders.

In vitro fertilization

The number of couples resorting to assisted reproductive technologies is constantly increasing. So, in 2011, 10,000 IVF procedures were performed according to CHI, and according to the results of last year – more than 65,000.

During this procedure, not one egg is used for fertilization, as with normal ovulation, but up to 15-20 oocytes at once. At each stage, there is an inevitable dropout, but 5-6 embryos are usually obtained at the exit. Among them, the embryologist chooses the most healthy embryo for implantation.

"Embryo selection" sounds creepy to an untrained ear, but not everything is as terrible as it may seem. It all starts with the fact that the characteristics of the embryo are morphologically evaluated, that is, how it looks externally, how well it develops, how correct the structure is at the time of transfer. This allows specialists to weed out embryos that can ultimately lead to miscarriage, frozen pregnancy and the birth of a child with pathology or genetic abnormalities.

It is at this stage that it becomes possible to conduct a genetic study of the embryo. There are several diagnostic methods. The first is PGD (preimplantation genetic diagnosis). It is used when one of the spouses or both spouses are carriers of anomalies that can lead to the appearance of a sufficiently large number of embryos with chromosomal rearrangements, resulting in the birth of children with developmental defects and intellectual disabilities. In the case when the mother's age exceeds 38 years, chromosomal abnormalities are observed in a significant proportion of embryos, and survival after implantation does not exceed 20%. Preimplantation diagnostics allows to bring this indicator up to 75% and practically exclude the birth of a child with chromosomal disorders.

The second way is to check for autosomal recessive diseases. If a carrier of mutations in both spouses is found in the family, then diagnostics is carried out at the stage of obtaining embryos in order to identify sick and healthy ones. The third method is PGS (preimplantation genetic screening). This happens when the parents have no abnormalities, but it is necessary to prevent mutations that occur during the transfer of genetic material.

In the absence of genetic control, on average, about 5% of pregnancies end with the birth of children with either chromosomal pathology or malformations, that is, about one in 200 newborns has chromosomal abnormalities.

During the IVF program, preimplantation screening is required to determine the chromosomal status of the embryo, which is the criterion for choosing an embryo for its transfer. The accuracy of the method is about 98%. This makes it possible to protect a married couple from pregnancy loss, reduce the risk of miscarriage, frozen pregnancy, or the birth of a child with genetic abnormalities.

Sperm donation

In the XXI century, unmarried women who dream of having a baby can resort to sperm donation to conceive a child. Before turning to this procedure, potential patients are wondering how to give birth to a healthy baby from a stranger, how safe it is, how to determine the quality of seminal fluid. In order to become a donor, a candidate undergoes examinations that include genetic tests. The scope of the examination is regulated, on the one hand, by legislation, that is, the mandatory minimum volume of tests. On the other hand, each clinic defines an additional list of examinations. It is mandatory for anyone who wants to be a donor to analyze the karyotype or chromosome set, in which there should be no deviations. Genetic counseling (pedigree analysis) is also carried out when we exclude any factors that alarm us. Additionally, autosomal recessive mutations are checked, for example, relatively common cystic fibrosis. At the request of the female patient, the donor sperm can be subjected to any genetic analysis, up to the complete decoding of the donor genome.

Any whim for your money?

Until now, it was about the prevention of genetic diseases. It must be said that the legislation of many European countries explicitly prohibits the selection of embryos according to some other criteria other than medical ones. Russian laws are more liberal: they have recently banned only the prediction of the sex of the implanted embryo. Nevertheless, advances in genetics already allow programming many characteristics of the unborn child, such as eye color. In the future, it is impossible to exclude the possibility of predicting complex traits determined by many genes, for example, height or IQ level. The only question is how ethical such selection is.

In 2009, 23andMe launched a service called "Inheritance Calculator". The program calculates the parameters of parents, such as eye color or intolerance to any product. In 2016, on this basis, the service "Designing a child" using IVF was developed. The couple fills out a questionnaire with wishes for the appearance of the unborn child. Reproductologists analyze the DNA of the mother and sperm donors in order to select the material that meets the specified criteria.

Stanford University professor Hank Greeley said that in 20-40 years, a new generation of people will emerge from engineered embryos. A married couple will donate seminal fluid and a piece of skin to the laboratory, from which eggs will be grown. According to the scientist, first doctors will reject genetic disorders, then risk genes for certain polygenic diseases, such as Alzheimer's disease, which by that time, hopefully, will be fully characterized. And then it will come to the selection of the external features of future children – the color of hair or eyes.

Of course, I am not a supporter of all children being created in laboratories, but if there is a risk of disease, future parents should resort to using reproductive technologies that are already available now. It can be assumed that at a certain level of development of these technologies, couples whose risk of conceiving a sick child will be increased will stop conceiving children naturally at all. If a couple has the opportunity to give birth to a healthy baby in the laboratory, why not eliminate the risk and resort to the help of reproductologists? I am sure that in this case, humanity can count on the fact that the risk of developing existing diseases will decrease to zero.

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